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Consensus molecular

R Michael Tuttle, Sukhjeet Ahuja, Anca M Avram, Victor Bernet, Patrick Bourguet, Gilbert H Daniels, Gary Dillehay, Ciprian Draganescu, Luca Giovanella, Glenn Flux, Dagmar Fuehrer, Bennett Greenspan, Markus Luster, Kristoff Muylle, Jan Smit, Douglas Van Nostrand, Frederik Verburg, Laszlo Hegedus
BACKGROUND: Publication of the 2015 American Thyroid Association (ATA) management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer was met with disagreement by the extended nuclear medicine community with regard to some of the recommendations related to the diagnostic and therapeutic use of radioiodine. Because of these concerns, the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI) declined to endorse the ATA guidelines...
March 22, 2019: Thyroid: Official Journal of the American Thyroid Association
Denis F Noubouossie, Brandi N Reeves, Brian D Strahl, Nigel S Key
Reactive and clonal neutrophil expansion has been associated with thrombosis, suggesting that neutrophils play a role in this process. However, while there is no doubt that activated monocytes trigger coagulation in a tissue factor-dependent manner, it remains uncertain whether stimulated neutrophils can also directly activate coagulation. After more than a decade of debate, it is now largely accepted that normal human neutrophils do not synthetize tissue factor, the initiator of the extrinsic pathway of coagulation...
March 21, 2019: Blood
Astrid Eijkelenboom, Bastiaan B J Tops, Anke van den Berg, Adrianus J C van den Brule, Winand N M Dinjens, Hendrikus J Dubbink, Arja Ter Elst, Willemina R R Geurts-Giele, Patricia J T A Groenen, Floris H Groenendijk, Daniëlle A M Heideman, Manon M H Huibers, Cornelis J J Huijsmans, Judith W M Jeuken, Léon C van Kempen, Esther Korpershoek, Leonie I Kroeze, Wendy W J de Leng, Carel J M van Noesel, Ernst-Jan M Speel, Maartje J Vogel, Tom van Wezel, Petra M Nederlof, Ed Schuuring, Marjolijn J L Ligtenberg
Next-generation sequencing (NGS) panel analysis on DNA from formalin-fixed paraffin-embedded (FFPE) tissue is increasingly used to also identify actionable copy number gains (gene amplifications) in addition to sequence variants. While guidelines for the reporting of sequence variants are available, guidance with respect to reporting copy number gains from gene-panel NGS data is limited. Here, we report on Dutch consensus recommendations obtained in the context of the national Predictive Analysis for THerapy (PATH) project, which aims to optimize and harmonize routine diagnostics in molecular pathology...
March 19, 2019: Virchows Archiv: An International Journal of Pathology
Jana Davina Debus, Hendrik Milting, Andreas Brodehl, Astrid Kassner, Dario Anselmetti, Jan Gummert, Anna Gaertner-Rommel
Arrhythmogenic right ventricular cardiomyopathy is a heritable cardiac disease causing severe ventricular arrhythmias, heart failure and sudden cardiac death. It is mainly caused by mutations in genes encoding several structural proteins of the cardiac desmosomes including the DSG2 gene encoding the desmosomal cadherin desmoglein-2. Although the molecular structure of the extracellular domain of desmoglein-2 is known, it remains an open question, how mutations in DSG2 contribute to the pathogenesis of arrhythmogenic right ventricular cardiomyopathy...
March 15, 2019: Journal of Molecular and Cellular Cardiology
Maria Z Tsimidou, Michaela Sotiroglou, Aspasia Mastralexi, Nikolaos Nenadis, Diego L García-González, Tullia Gallina Toschi
An ongoing challenge in olive oil analytics is the development of a reliable procedure that can draw the consensus of all interested parties regarding the quantification of concentrations above the required minimum value of 5 mg of bioactive "olive oil polyphenols" per 20 g of the oil, to fulfill the health claim introduced by the European Commission (EC) Regulation 432/2012. An in-house validated ultra-high performance liquid chromatography (UHPLC) protocol fit for this purpose is proposed. It relies on quantification of the total hydroxytyrsol (Htyr) and tyrosol (Tyr) content in the virgin olive oil (VOO) polar fraction (PF) before and after acidic hydrolysis of their bound forms...
March 16, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Fan Wu, Rui-Chao Chai, Zhiliang Wang, Yu-Qing Liu, Zheng Zhao, Guan-Zhang Li, Hao-Yu Jiang
Isocitrate dehydrogenase (IDH) mutant glioblastoma (GBM), accounts for ~10% GBMs, arises from lower grade diffuse glioma and preferentially appears in younger patients. Here, we aim to establish a robust gene expression-based molecular classification of IDH-mutant GBM. A total of 33 samples from the Chinese Glioma Genome Atlas RNA-sequencing data were selected as training set, and 21 cases from Chinese Glioma Genome Atlas microarray data were used as validation set. Consensus clustering identified three groups with distinguished prognostic and molecular features...
February 13, 2019: Carcinogenesis
Kumar Prabhash, Suresh H Advani, Ullas Batra, Bivas Biswas, Anuradha Chougule, Mithua Ghosh, Vamshi Krishna Muddu, T P Sahoo, Ashok K Vaid
Novel molecular targets and promising targeted therapies have reshaped diagnostics in patients with advanced non-small cell lung cancer (NSCLC). Despite this progress, the implementation of molecular screening to identify predictive biomarkers in Indian clinical and pathology settings has been challenging due to operational and logistical constraints. This consensus guideline brings together medical oncologists, molecular pathologists and pathologists from India to provide a quick and competent reference for biomarker testing in NSCLC...
March 12, 2019: Advances in Therapy
Sara Cherradi, Pierre Martineau, Céline Gongora, Maguy Del Rio
Purpose: Colorectal cancer (CRC) is a heterogeneous disease that can be classified into distinct molecular subtypes. The aims of this study were 1) to compare claudin ( CLDN ) gene expression in CRC samples and normal colon mucosa, and then in the different CRC molecular subtypes, and 2) to assess their prognostic value. Patients and methods: CLDN expression in CRC samples was analyzed using gene expression data for a cohort of 143 primary CRC samples, and compared in the same CRC samples classified into different molecular subtypes (C1 to C6 according to the Marisa's classification, and CMS1 to CMS4 of the consensus classification)...
2019: Cancer Management and Research
Mehmet Akce, Bassel F El-Rayes
Neoadjuvant chemoradiotherapy followed by surgical resection is the standard of care for locally advanced rectal adenocarcinoma. Up to one third of patients achieve pathologic complete response (CR) with neoadjuvant therapy. Promising disease-free and overall survival outcomes have been reported in patients who achieve clinical CR after neoadjuvant therapy without surgical resection. Furthermore, patients who have local recurrence have acceptable disease control outcomes with salvage resection. With consideration of morbidities associated with surgical resection and similar clinical outcomes, interest in nonsurgical management of low rectal cancers has emerged...
March 2019: Journal of Oncology Practice
Vani Santosh, Palavalasa Sravya, Tejpal Gupta, Dattatraya Muzumdar, Geeta Chacko, Vaishali Suri, Sridhar Epari, Anandh Balasubramaniam, Bishan Dass Radotra, Sandip Chatterjee, Chitra Sarkar, Rakesh Jalali
Introduction: Recent advances in the molecular biology of adult diffuse gliomas have brought about a paradigm shift in their diagnostic criteria, as witnessed in the World Health Organization (WHO) 2016 guidelines for central nervous system tumors. It is now mandatory to perform several molecular tests to reach a definitive integrated diagnosis in most of the cases. This comes with additional cost and higher turnaround time, which is not always affordable in developing countries like India...
January 2019: Neurology India
Alexandra N Willauer, Yusha Liu, Allan A L Pereira, Michael Lam, Jeffrey S Morris, Kanwal P S Raghav, Van K Morris, David Menter, Russell Broaddus, Funda Meric-Bernstam, Andrea Hayes-Jordan, Winston Huh, Michael J Overman, Scott Kopetz, Jonathan M Loree
BACKGROUND: Colorectal cancer (CRC) incidence is increasing in adults younger than 50 years. This study evaluated clinical and molecular features to identify those features unique to early-onset CRC that differentiate these patients from patients 50 years old or older. METHODS: Baseline characteristics were evaluated according to the CRC onset age with 3 independent cohorts. A fourth cohort was used to describe the impact of age on the consensus molecular subtype (CMS) prevalence...
March 11, 2019: Cancer
Emily Cannon, Steven Buechler
BACKGROUND: Cancers of the right colon have been shown to differ from left-side colon cancers in prognosis, response to epithelial growth factor receptor inhibitors, microsatellite instability and BRAF mutation status, and other molecular characteristics. Clinical application of these differences will benefit from a deeper understanding of how tumor location defines and is defined by gene expression. MATERIALS AND METHODS: This study was carried out using Affymetrix microarray datasets (Cohort A: training set, n = 352; validation set, n = 519) and samples from The Cancer Genome Atlas Colon Adenocarcinoma database (Cohort B: n = 408), in which tumor location was reported...
February 14, 2019: Clinical Colorectal Cancer
Elena Sendagorta-Cudós, Joaquín Burgos-Cibrián, Manuel Rodríguez-Iglesias
The Human Papillomavirus (HPV) is a double-stranded DNA virus, with more than 200 different genotypes having been identified. This infection is considered the most common sexually transmitted infection (STI), and it is the cause of a significant number of diseases, both benign lesions (anogenital condylomas) and pre-malignant lesions and different cancers. The diagnosis of the infection is performed by molecular techniques based on the detection of viral DNA, the mRNA of oncogenic proteins and cellular alteration caused by the infection...
March 7, 2019: Enfermedades Infecciosas y Microbiología Clínica
Joost L Boormans, Ellen C Zwarthoff, Peter C Black, Peter J Goebell, Ashish M Kamat, Roman Nawroth, Roland Seiler, Stephen B Williams, Bernd J Schmitz-Dräger
The 16th Meeting of the International Bladder Cancer Network (IBCN) took place from October 11 to 13, 2018 in Rotterdam, the Netherlands. As in the previous year, muscle-invasive bladder cancer (MIBC) was the main topic of the congress based upon the rapid evolution in this field over the last several years. This year´s meeting was dominated by presentations focusing on genomic subtyping in MIBC and identification of novel therapeutic targets. These topics were complemented by submissions on immunotherapy, a variety of clinical topics, and biomarker research...
March 7, 2019: Urologic Oncology
Masato Yozu, M Priyanthi Kumarasinghe, Ian S Brown, Anthony J Gill, Christophe Rosty
Lynch syndrome is the most common hereditary form of colorectal carcinoma caused by a constitutional pathogenic mutation in a DNA mismatch repair gene. Identifying Lynch syndrome is essential to initiate intensive surveillance program for the patient and affected relatives. On behalf of the Australasian Gastrointestinal Pathology Society (AGPS), we present in this manuscript consensus guidelines for Lynch syndrome screening in patients with colorectal carcinoma. The goal of this consensus document is to provide recommendations to pathologists for diagnosis of Lynch syndrome with discussion of the benefits and limitations of each test...
March 6, 2019: Pathology
Gonzalo Izaguirre, Marcelino Arciniega, Andrea G Quezada
The molecular determinants of substrate specificity and selectivity in the proprotein convertase (PC) family of proteases are poorly understood. Here we demonstrate that the natural serpin family inhibitor, serpin B8, is a specific and selective inhibitor of furin relative to the other PCs of the constitutive protein secretion pathway, PC4, PC5, PACE4, and PC7 (PC4-PC7, respectively), and identify reactive-site (P6-P5' residues) and exosite elements of the serpin that contribute to this specificity and selectivity through studies of chimeras of serpin B8 and α1PDX, an engineered serpin inhibitor of furin...
March 8, 2019: Biochemistry
Stefano Santabarbara, Anna Paola Casazza, Gary Hastings
Uncovering the parameters underlying the electron transfer (ET) in photosynthetic reaction centres is of importance for understanding the molecular mechanisms underpinning their functionality. The reductive nature of most cofactors involved in photosynthetic ET makes the direct estimation of their properties difficult. Photosystem I (PSI) operate in a highly reducing regime, making the assessment of cofactor properties even more difficult. Kinetic modelling coupled to a non-adiabatic description of ET is a useful approach in overcoming this hindrance...
March 7, 2019: Physiologia Plantarum
Jinkyung Kim, Sung-Min Kang, Su Young Oh, Heon-Jin Lee, Inhan Lee, Jae-Chan Hwang, Su-Hyung Hong
NGFI-A binding protein 2 (NAB2) represses the transcriptional activation of early growth response protein-1 (EGR1), a tumor-suppressor. However, Epidermal Growth Factor (EGF) promotes tumor progression even with significant EGR1 upregulation. The molecular mechanism through which NAB2 is involved in cancer is largely unknown. Therefore, we evaluated how the NAB2-mediated suppression of EGR1 facilitates head and neck squamous cell carcinoma (HNSCC) cancer progression, in association with Sp1, which competes with EGR1 as a transcriptional regulator...
March 6, 2019: Cancers
Lisa E Creary, Sandra G Guerra, Winnie Chong, Colin J Brown, Thomas R Turner, James Robinson, Will P Bultitude, Neema P Mayor, Steven G E Marsh, Katsuyuki Saito, Kevin Lam, Jamie L Duke, Timothy L Mosbruger, Deborah Ferriola, Dimitrios Monos, Amanda Willis, Medhat Askar, Gottfried Fischer, Chee Loong Saw, Ioannis Ragoussis, Martin Petrek, Carles Serra-Pagés, Manel Juan Otero, Catherine Stavropoulos-Giokas, Amalia Dinou, Reem Ameen, Salem Al Shemmari, Eric Spierings, Ketevan Gendzekhadze, Gerald P Morris, Quiheng Zhang, Zahra Kashi, Susan Hsu, Sridevi Gangavarapu, Kalyan C Mallempati, Fumiko Yamamoto, Kazutoyo Osoegawa, Tamara Vayntrub, Chia-Jung Chang, John A Hansen, Marcelo A Fernández-Viňa
Extended molecular characterization of HLA genes in the IHWG reference B-lymphoblastoid cell lines (B-LCLs) was one of the major goals for the 17th International HLA and Immunogenetics Workshop (IHIW). Although reference B-LCLs have been examined extensively in previous workshops complete high-resolution typing was not completed for all the classical class I and class II HLA genes. To address this, we conducted a single-blind study where select panels of B-LCL genomic DNA samples were distributed to multiple laboratories for HLA genotyping by next-generation sequencing methods...
March 4, 2019: Human Immunology
Francisca Wood Ortiz, Yuri V Sergeev
Multidomain proteins account for 70% of the eukaryotic proteome. In genetic disease, multidomain proteins are often affected by numerous mutations, but the effects of these mutations on protein stability and their roles in genetic disease are not well understood. Here, we analyzed protein globular domains to understand how genetic mutations affect the stability of multidomain proteins in inherited disease. In total, 291 domain atomic structures from nine multidomain proteins were modeled by homology, equilibrated using molecular dynamics in water, and subjected to global computational mutagenesis...
March 6, 2019: Scientific Reports
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